Carbonyl stress caused by reactive
carbonyl species (RCS) is closely
related to various brain diseases. As the highly reactive, highly
toxic, and lipophilic RCS, malondialdehyde (MDA) and formaldehyde
(FA) could easily cross the blood–brain barrier (BBB) and induce
protein dysfunction or cross-linking in the brain. Do MDA and FA coordinately
regulate the physio-pathological processes of the brain? To answer
the question, first of all, powerful identification and sensing tools
are needed. However, competent probes for simultaneously analyzing
MDA and FA in living brains are lacking, which originates from the
following three challenges: (1) MDA and FA are difficult to distinguish
due to their great similarity in structure and reactivity; (2) to
achieve simultaneous and discriminable imaging, same excitation and
different emissions are preferable; and (3) the detection of MDA and
FA in living brains require the materials to pass through the BBB.
Thus, we created a two-photon fluorescent agent, TFCH, for MDA/FA.
The hydrazine group in TFCH could successfully differentiate MDA/FA
at 440/510 nm under same excitation. Moreover, the lipophilic trifluoromethyl
group (−CF3) in TFCH prompts it to traverse the
BBB, thereby realizing the coinstantaneous visualization of MDA and
FA in the living brain. Using TFCH, we observed the excessive production
of MDA and FA in living PC12 cells under carbonyl stress and oxidative
stress. Notably, for the first time, two-photon fluorescence imaging
indicated the synchronous increase of MDA and FA in living brains
of mice with depression. Altogether, this work provides a promising
tool for revealing the carbonyl stress-related molecular mechanism
involved in brain diseases.